Increasing evidence suggests that insulin dependent diabetes is the result of one or more defects involving the pancreatic beta cells. The objective of this project is to elucidate further the physiology, biochemistry and morphology of pancreatic islet cells, and to determine the possible role of immune factors in causing beta cell damage in diabetes. Three areas will be investigated: 1) continuous clonal lines of rat pancreatic islet cells developed in our laboratory will be further characterized. These cells will be used in a variety of studies including preparation of somatic cell hybrids and examination of the role of paracrine influences in regulating insulin secretion; 2) the etiology of insulitis and beta cell damage in the spontaneously diabetic BB rat will be studied. The role of cell and antibody mediated cytotoxicity will be examined using chromium-51 labeled beta cell targets and lymphocyte effector cells from BB rats with acute insulitis; 3) the possible role of DNA methylation in controlling insulin gene expression will be examined.